Typhoid Vaccine Live Oral (Systemic)

Note: This monograph is specific for the typhoid vaccine prepared with the Salmonella typhi Ty21a strain.

Commonly used brand name(s): Vivotif Berna.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Category:

Immunizing agent (active)—

IndicationsAccepted

Salmonella typhi infection (prophylaxis)—Typhoid vaccine is indicated for immunization of adults and children 6 years of age and older against disease caused by Salmonella typhi{10}.
—Routine typhoid vaccination is no longer recommended in the U.S. {10}{12} However, selective vaccination is indicated for the following groups: • Travelers to areas that have a recognized risk of exposure to S. typhi{10}{12}. Risk is greatest for travelers to developing countries (especially countries in Latin America, Asia, and Africa) who have prolonged exposure to potentially contaminated food and drink {06}{10}{12}. Such travelers should be cautioned that typhoid vaccine is not a substitute for careful selection of food and drink, since the vaccine is not 100% effective and the protection it offers can be overwhelmed by large inocula of S. typhi{06}{10}{12}.
• Persons with intimate exposure, such as continued household contact, to a documented typhoid fever carrier {06}{10}{12}.
• Workers in microbiology laboratories who frequently work with S. typhi{06}{10}{12}.

—An optimal booster dose has not yet been established {10}. However, it is recommended that a booster dose consisting of 4 vaccine capsules taken on alternate days be given every 5 years if there is repeated or continued exposure to typhoid fever {10}.
—Routine vaccination of sewage sanitation workers is warranted only in areas with endemic typhoid fever {06}{12}. There is no evidence that typhoid vaccine is useful in controlling common-source outbreaks {10}{12}. Also, the use of typhoid vaccine is not indicated for persons attending rural summer camps or in areas in which natural disasters, such as floods, have occurred {10}{12}.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:Source—
Typhoid vaccine Ty21a is a live attenuated vaccine for oral administration {10}{12}. The vaccine contains the attenuated strain Salmonella typhi Ty21a {10}{12}. The vaccine strain is grown under controlled conditions in a medium containing dextrose, galactose, a digest of bovine tissues, and an acid digest of casein {10}. The bacteria are collected by centrifugation, mixed with a stabilizer containing lactose and amino acids, and then lyophilized {10}. The lyophilized bacteria mixture is placed in gelatin capsules, which are coated with an organic solution to render them resistant to dissolution by stomach acids {10}.Mechanism of action/Effect:

The precise mechanism by which typhoid vaccine Ty21a confers protection against typhoid fever is unknown {10}{12}. However, it is known that immunization of adult subjects can elicit a humoral anti–S. typhi lipopolysaccharide (LPS) antibody response {03}{04}{10}{12}.

This vaccine will not afford protection against species of Salmonella , other than Salmonella typhi , or against other bacteria that cause enteric disease {10}.

The ability of S. typhi to cause disease and induce a protective immune response is dependent upon the bacteria possessing a complete LPS {10}. The S. typhi Ty21a vaccine strain, because of a reduction in enzymes essential for LPS biosynthesis, is restricted in its ability to produce complete LPS {03}{04}{10}. However, enough complete LPS is synthesized to induce a protective immune response {03}{10} Despite the low levels of LPS synthesis, the cells lyse before regaining a virulent phenotype. {03}{04}{10}. This occurs because of the intracellular build-up of toxic metabolic intermediates during LPS synthesis {04}{06}{10}.

Protective effect

Vaccine efficacy is approximately 65% and is {16} similar to the efficacy of the heat-phenol-inactivated injectable typhoid vaccine, which is 51 to 77% {03}{05}{06}{07}{12}.

Time to protective effect

Immunization (ingestion of all 4 doses of the vaccine) should be completed at least 1 week prior to potential exposure to S. typhi{10}.

Duration of protective effect

Follow-up studies of vaccine trial subjects showed continued efficacy 5 to 7 years after immunization {06}{10}{12}{16}.Elimination:
At the recommended dosage, the S. typhi Ty21a vaccine strain is not excreted in the feces {10}{12}. However, clinical studies in volunteers have shown that overdosing can increase the possibility of shedding the S. typhi Ty21a vaccine strain in the feces {03}{10}.

Precautions to ConsiderCarcinogenicity/Mutagenicity

Long-term studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of this vaccine {10}.Pregnancy/Reproduction
Fertility—
Studies have not been done in humans or animals {10}{12}.

Pregnancy—
It is recommended that the vaccine be administered during pregnancy only if clearly needed {06}{10}.

It is not known whether typhoid vaccine is excreted in breast milk {10}. However, problems in humans have not been documented.Pediatrics

Appropriate studies on the relationship of age to the effects of the vaccine have not been performed in infants and children up to 6 years of age {10}. Safety and efficacy have not been established and use is not recommended {10}.

Geriatrics

Appropriate studies on the relationship of age to the effects of typhoid vaccine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antibacterials, systemic, or{04}{09}{10}{16}» Antimalarials{16} (concurrent use of systemic antibacterials {10}{16} or antimalarials {16} with typhoid vaccine may prevent the vaccine bacteria from multiplying sufficiently to induce a protective immune response; antimalarials should be administered 24 hours prior to administration of the typhoid vaccine {16})

» Immunosuppressive agents or{10}{15}{18}» Radiation therapy{15}{16}{18} (because normal defense mechanisms are suppressed, concurrent use with live oral typhoid vaccine may potentiate the replication of the vaccine bacteria, may increase the side/adverse effects of the vaccine, and/or may decrease the patient's antibody response to the vaccine {15}{16}. The precaution does not apply to corticosteroids used as replacement therapy, for short-term [less than 2 weeks] systemic therapy, or by other routes of administration that do not cause immunosuppression {15}{16})

Live vaccines, other{15}{16} (when live virus vaccines are administered on different days within 1 month of each other, the chance exists that the immune response may be impaired; therefore, live virus vaccines not administered on the same day should be given at least 1 month apart; there is no consensus among USP medical experts that the same would apply to live bacterial vaccines {16})

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problems exist:» Diarrhea, persistent, or{10}» Febrile illness, acute, or{06}{10}» Gastrointestinal illness, acute, or{10}» Vomiting, persistent{10} (administration of live oral typhoid vaccine should be postponed or avoided, since acute illnesses may interfere with the replication of typhoid vaccine bacteria and therefore with final immunity {16}; minor illnesses, such as mild upper respiratory infections, do not preclude administration of vaccine {15}{16})

» Immune deficiency conditions, congential or hereditary, or{06}{10}{12}{15}{16}» Immune deficiency conditions, primary or acquired{06}{10}{12}{15} (because of reduced or suppressed defense mechanisms, the use of live oral typhoid vaccine may potentiate the replication of the vaccine bacteria, may increase the side/adverse effects of the vaccine, and/or may decrease the patient's antibody response to the vaccine {15}{16}{18})

Risk-benefit should be considered when the following medical problems exist
Sensitivity to live oral typhoid vaccine, sucrose, lactose, or beef{06}{10} ; however, a history of a severe reaction to the parenteral typhoid vaccine is not a precaution for receiving the live oral vaccine{06}{16}

Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:Those indicating need for medical attentionIncidence rareAnaphylactic reaction (difficulty in breathing or swallowing; hives; itching, especially of soles or palms; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; sudden and severe unusual tiredness or weakness)

Leaving vaccine at room temperature will cause it to lose its effectiveness

Taking dose approximately 1 hour before a meal; taking with a cold or lukewarm drink (temperature not to exceed body temperature, e.g., 37 °C [98.6 °F])

Swallowing capsule whole and as soon as possible after placing in mouth; not chewing capsule
Missed dose: If remembered on the day it should be taken, taking as directed; however, if not remembered until the next day, taking the missed dose at that time and rescheduling your every-other-day doses from then {16}; it is essential that vaccine be taken exactly as directed to get the most protection against typhoid fever {16}

» Proper storage: Keeping vaccine refrigerated at all times; replacing unused vaccine in the refrigerator between dosesPrecautions while using this medication
Checking with physician before receiving:

General Dosing Information
Immunization (ingestion of all 4 doses of the vaccine) should be completed at least 1 week prior to potential exposure to S. typhi{10}.

Since this is an enteric dosage form, the vaccine capsules should be inspected to ensure that the foil seal and capsules are intact {10}; any that are damaged should be replaced.

Each enteric-coated capsule should be swallowed with a cold or lukewarm drink (temperature not to exceed 37 °C [98.6 °F], i.e., body temperature), approximately 1 hour before a meal on alternate days (days 1, 3, 5, and 7) for a total of 4 doses {10}{12}.

The vaccine capsule should not be chewed and should be swallowed as soon as possible after it is placed in the mouth {10}.

A complete immunization schedule is the ingestion of 4 vaccine capsules, as directed {10}{16}. Unless this schedule is followed, an optimal immune response may not be achieved {10}.

Even if the complete immunization schedule is followed, not all recipients of the vaccine will be fully protected against typhoid fever {10}. Travelers should take all necessary precautions to avoid contact with, or ingestion of, potentially contaminated food or water {10}.

The optimal booster schedule for the live oral typhoid vaccine has not been determined {10}{12}. However, efficacy has been shown to persist for 5 to 7 years after administration of a complete primary immunization {06}{10}{12}. Therefore, it is recommended that a booster dose of 4 vaccine capsules taken on alternate days be given every 5 years if repeated or continued exposure to S. typhi occurs {06}{10}.

There is no experience with the use of the live oral typhoid vaccine as a booster in persons previously immunized with parenteral typhoid vaccine {06}{10}{12}. However, if repeated or continued exposure to S. typhi occurs, booster doses of the parenteral vaccine are recommended every 3 years to maintain immunity after vaccination with parenteral typhoid vaccine {06}{12}. Even if more than 3 years have elapsed since the prior parenteral vaccination, a single booster dose of the parenteral vaccine is sufficient {06}{12}. Therefore, it appears that using the primary series of 4 doses of live oral typhoid vaccine as a booster for persons previously vaccinated with the parenteral vaccine is a reasonable alternative to administration of a parenteral booster {06}{12}.

For treatment of adverse effects

Recommended treatment consists of the following:For adults

• If anaphylaxis occurs, 0.2 to 0.5 mg of epinephrine (base) may be administered intramuscularly or subcutaneously, the dose being repeated every 10 to 15 minutes as needed {01}. The dosage may be increased up to a maximum of 1 mg per dose, if necessary {01}.
• If anaphylactic shock occurs: —0.5 mg of epinephrine (base) may be administered initially intramuscularly or subcutaneously, the dose being repeated every 5 minutes if necessary {01}. If there is an inadequate response to the intramuscular or subcutaneous dose, 0.025 to 0.05 mg of epinephrine (base) may be administered intravenously every 5 to 15 minutes as needed {01}.
—Alternatively, 0.1 to 0.25 mg of epinephrine (base) may be administered slowly by intravenous injection {01}. The dose may be repeated every 5 to 15 minutes as needed or followed by an intravenous infusion at an initial rate of 0.001 mg per minute, the rate being increased to 0.004 mg per minute if necessary {01}.

For children

• If anaphylaxis occurs, 0.01 mg of epinephrine (base) per kg of body weight or 0.3 mg of epinephrine (base) per square meter of body surface, up to a maximum of 0.5 mg per dose, may be administered subcutaneously, the dose being repeated every 15 minutes for 2 doses, then administered every 4 hours as needed {01}.
• If anaphylactic shock occurs, 0.01 mg of epinephrine (base) per kg of body weight, up to a maximum of 0.3 mg, may be administered intramuscularly or subcutaneously, the dose being repeated every 5 minutes if necessary {01}. If there is an inadequate response to the intramuscular or subcutaneous dosage, 0.01 mg of epinephrine (base) per kg of body weight may be administered intravenously every 5 to 15 minutes as needed {01}.

Oral Dosage FormsTYPHOID VACCINE LIVE ORAL{16} ENTERIC-COATED CAPSULESUsual adult and adolescent dose
Oral, 1 capsule every other day for a total of four doses {10}{12}.Usual pediatric dose
Infants and children up to 6 years of age—Safety and efficacy have not been established; use is not recommended {10}{12}.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F) {10}.Stability:
Typhoid vaccine is not stable when exposed to ambient temperatures. The vaccine should therefore be shipped and stored between 2 and 8 °C (36 and 46 °F). Each package of vaccine shows an expiration date. This expiration date is valid only if the product has been maintained at 2 to 8 °C (36 to 46 °F) {10}.Auxiliary labeling:
• Keep refrigerated at all times {10}.
• Swallow capsules whole {10}.

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